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Post-doc position: Characterization of molecular determinants and cellular pathways controlling muscle fiber splitting

on the July 21, 2020

In advanced stages of muscular dystrophies, including Duchenne Muscular Dystrophy (DMD), a large subset of muscle fibers shows longitudinal splitting or branching. However, despite critical impact on muscle cytoarchitecture, on vulnerability to contraction-induced damage and on muscle weakening, mechanisms of muscle fibers splitting remain largely unexplored. The goal of this project is to identify molecular determinants and characterize cellular pathways controlling muscle fiber splitting.

Our preliminary data in Drosophila model (Bertin  et  al.,  bioRxiv,  2019) indicate  that affected  muscle identity information and/or locally induced excessive myoblast fusion could result in split muscle phenotype. Consistent with thisobservation, we identified Gelsolin as muscle identity realisator gene, which acts to limit fusion events and prevents muscles from splitting. Gelsolin belongs to the conserved family of  actin severing proteins whose impact on muscle formation remains unknown. Within this project it is expected to:

  • i) apply Drosophila model to functionally dissectthe role of Gelsolin and Gelsolin-like  proteins  in  regulation  of  myoblast  fusion  arrest  and in preventing  split phenotype; 
  • ii)  analyse single nuclei RNAseq data sets from split fibers of mdx mutant mice (collaboration with C. Birchmeier, MDC Berlin) and determine associated gene  expression signature(s); 
  • iii) analyse functionally the potential mdx-split hits in Drosophila model and on the  “split  fiber  on  the  dish”  system of differentiated iPSCs (collaboration with  O.  Pourquié, Harvard, Boston).


Motivated candidates with background in Drosophila genetics, the main experimental model, and/or in developmental muscle biology, are encouraged to apply.
iGReD is highly  dynamic  biomedical  research  institute  with  up  to  date  imaging  and model organisms platforms and stimulating scientific environment.

Position is available for 2 years, from October 2020 with a possibility of extension.

Clermont-Ferrand  is  located  in  the  center  of  France in the heart of the  « Chaîne  des Puys » vulcanoes – The UNESCO World Heritage Center.
 

Send your application (motivation letter with  indication of contacts for reference) to christophe.jagla@uca.fr before September 1st, 2020.

Published on July 28, 2020